University of Oulu

Schlosser, P., Tin, A., Matias-Garcia, P.R. et al. Meta-analyses identify DNA methylation associated with kidney function and damage. Nat Commun 12, 7174 (2021). https://doi.org/10.1038/s41467-021-27234-3

Meta-analyses identify DNA methylation associated with kidney function and damage

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Author: Schlosser, Pascal1,2,3; Tin, Adrienne3,4; Matias-Garcia, Pamela R.5,6,7;
Thio, Chris H. L.8; Joehanes, Roby9,10; Liu, Hongbo11; Weihs, Antoine12; Yu, Zhi13,14,15; Hoppmann, Anselm1,2; Grundner-Culemann, Franziska1,2; Min, Josine L.16,17; Adeyemo, Adebowale A.18; Agyemang, Charles19; Arnlov, Johan20,21; Aziz, Nasir A.22,23; Baccarelli, Andrea24; Bochud, Murielle25; Brenner, Hermann26,27,28,29,30; Breteler, Monique M. B.22,31; Carmeli, Cristian25,32; Chaker, Layal33,34; Chambers, John C.35,36,37,38; Cole, Shelley A.39; Coresh, Josef3; Corre, Tanguy25; Correa, Adolfo4; Cox, Simon R.40; de Klein, Niek41; Delgado, Graciela E.42; Domingo-Relloso, Arce43,44,45; Eckardt, Kai-Uwe46,47; Ekici, Arif B.48; Endlich, Karlhans49,50; Evans, Kathryn L.51; Floyd, James S.52,53,54; Fornage, Myriam55,56; Franke, Lude41,57; Fraszczyk, Eliza8; Gao, Xu24,58; Gao, Xin26; Ghanbari, Mohsen33; Ghasemi, Sahar12,50,59; Gieger, Christian5,6; Greenland, Philip60; Grove, Megan L.56; Harris, Sarah E.40; Hemani, Gibran16,17; Henneman, Peter61; Herder, Christian62,63,64,65; Horvath, Steve66,67; Hou, Lifang60; Hurme, Mikko A.68; Hwang, Shih-Jen9,69; Järvelin, Marjo-Riitta70,71,72,73; Kardia, Sharon L. R.74; Kasela, Silva75; Kleber, Marcus E.42,76; Koenig, Wolfgang77,78,79; Kooner, Jaspal S.37,38,80; Kramer, Holly81,82,83; Kronenberg, Florian84; Kuhnel, Brigitte5,6; Lehtimaki, Terho85,86,87; Lind, Lars88; Liu, Dan22; Liu, Yongmei89; Lloyd-Jones, Donald M.60; Lohman, Kurt89; Lorkowski, Stefan90,91; Lu, Ake T.66; Marioni, Riccardo E.51; Marz, Winfried42,91,92,93; McCartney, Daniel L.51; Meeks, Karlijn A. C.18,19; Milani, Lili75; Mishra, Pashupati P.85,86,87; Nauck, Matthias50,94; Navas-Acien, Ana44; Nowak, Christoph20; Peters, Annette6,95; Prokisch, Holger96,97; Psaty, Bruce M.52,53,54,98; Raitakari, Olli T.99,100,101,102; Ratliff, Scott M.74; Reiner, Alex P.53; Rosas, Sylvia E.103,104; Schottker, Ben26,27; Schwartz, Joel105; Sedaghat, Sanaz106; Smith, Jennifer A.81,82,85,107; Sotoodehnia, Nona54; Stocker, Hannah R.26,27; Stringhini, Silvia25; Sundstrom, Johan88,108; Swenson, Brenton R.54,109; Tellez-Plaza, Maria43; van Meurs, Joyce B. J.34; van Vliet-Ostaptchouk, Jana V.110; Venema, Andrea61; Verweij, Niek111; Walker, Rosie M.51; Wielscher, Matthias70; Winkelmann, Juliane96,112,113,114; Wolffenbuttel, Bruce H. R.110; Zhao, Wei74; Zheng, Yinan60; Loh, Marie35,36; Snieder, Harold8; Levy, Daniel9,10; Waldenberger, Melanie5,6,78; Susztak, Katalin11; Kottgen, Anna1,2,3; Teumer, Alexander50,59,115
Organizations: 1Univ Freiburg, Inst Genet Epidemiol, Fac Med, Freiburg, Germany.
2Univ Freiburg, Med Ctr, Freiburg, Germany.
3Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA.
4Univ Mississippi, Med Ctr, Dept Med, Jackson, MS 39216 USA.
5German Res Ctr Environm Hlth, Res Unit Mol Epidemiol, Helmholtz Zentrum Munchen, D-85764 Neuherberg, Bavaria, Germany.
6German Res Ctr Environm Hlth, Inst Epidemiol, Helmholtz Zentrum Munchen, D-85764 Neuherberg, Bavaria, Germany.
7Tech Univ Munich, TUM Sch Med, Munich, Germany.
8Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, Groningen, Netherlands.
9Framingham Heart Dis Epidemiol Study, Framingham, MA USA.
10NHLBI, Populat Sci Branch, NIH, Bldg 10, Bethesda, MD 20892 USA.
11Univ Penn, Perelman Sch Med, Dept Med & Genet, Philadelphia, PA 19104 USA.
12Univ Med Greifswald, Dept Psychiat & Psychotherapy, Greifswald, Germany.
13Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.
14Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.
15Massachusetts Gen Hosp, Ctr Genom Med, Boston, MA 02114 USA.
16Univ Bristol, MRC Integrat Epidemiol Unit, Bristol, Avon, England.
17Univ Bristol, Bristol Med Sch, Populat Hlth Sci, Bristol, Avon, England.
18NHGRI, Ctr Res Genom & Global Hlth, NIH, Bethesda, MD 20892 USA.
19Univ Amsterdam, Amsterdam Univ Med Ctr, Amsterdam Publ Hlth Res Inst, Dept Publ & Occupat Hlth, NL-1105 AZ Amsterdam, Netherlands.
20Karolinska Inst, Family Med & Primary Care Unit, Dept Neurobiol Care Sci & Soc NVS, Huddinge, Sweden.
21Dalarna Univ, Sch Hlth & Social Studies, Falun, Sweden.
22German Ctr Neurodegenerat Dis DZNE, Populat Hlth Sci, Bonn, Germany.
23Univ Bonn, Dept Neurol, Fac Med, Bonn, Germany.
24Columbia Univ, Mailman Sch Publ Hlth, Lab Environm Precis Hlth, New York, NY USA.
25Univ Lausanne, Ctr Primary Care & Publ Hlth Unisante, Lausanne, Switzerland.
26German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany.
27Heidelberg Univ, Network Aging Res, Heidelberg, Germany.
28German Canc Res Ctr, Div Prevent Oncol, Heidelberg, Germany.
29Natl Ctr Tumor Dis NCT, Heidelberg, Germany.
30German Canc Res Ctr, German Canc Consortium, Heidelberg, Germany.
31Univ Bonn, Inst Med Biometry Informat & Epidemiol IMBIE, Fac Med, Bonn, Germany.
32Univ Fribourg, Populat Hlth Lab, Fribourg, Switzerland.
33Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.
34Erasmus MC, Dept Internal Med, Rotterdam, Netherlands.
35Nanyang Technol Univ, Lee Kong Chian Sch Med, Singapore, Singapore.
36Imperial Coll London, Dept Epidemiol & Biostat, London, England.
37London North West Healthcare NHS Trust, Ealing Hosp, Dept Cardiol, Southall, Middx, England.
38Imperial Coll Healthcare NHS Trust, London, England.
39Texas Biomed Res Inst, San Antonio, TX USA.
40Univ Edinburgh, Dept Psychol, Lothian Birth Cohorts Grp, 7 George Sq, Edinburgh EH8 9JZ, Midlothian, Scotland.
41Univ Groningen, Univ Med Ctr Groningen, Dept Genet, Hanzepl 1, Groningen, Netherlands.
42Heidelberg Univ, Med Fac Mannheim, Dept Med 5, Mannheim, Germany.
43Carlos III Hlth Inst, Natl Ctr Epidemiol, Dept Chron Dis Epidemiol, Madrid, Spain.
44Columbia Univ, Dept Environm Hlth Sci, Mailman Sch Publ Hlth, New York, NY USA.
45Univ Valencia, Dept Stat & Operat Res, Valencia, Spain.
46Univ Erlangen Nurnberg, Dept Nephrol & Hypertens, Erlangen, Germany.
47Charite Univ Med Berlin, Dept Nephrol & Med Intens Care, Berlin, Germany.
48Friedrich Alexander Univ Erlangen Nurnberg, Inst Human Genet, D-91054 Erlangen, Germany.
49Univ Med Greifswald, Dept Anat & Cell Biol, Greifswald, Germany.
50DZHK German Ctr Cardiovasc Res, Partner Site Greifswald, Greifswald, Germany.
51Univ Edinburgh, Inst Genet & Canc, Ctr Genom & Expt Med, Edinburgh EH4 2XU, Midlothian, Scotland.
52Univ Washington, Dept Med, Seattle, WA 98101 USA.
53Univ Washington, Dept Epidemiol, Seattle, WA 98101 USA.
54Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98101 USA.
55McGovern Med Sch, Brown Fdn, Inst Mol Med, Houston, TX 77030 USA.
56Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Dept Epidemiol Human Genet & Environm Sci, Ctr Human Genet, Houston, TX 77030 USA.
57Oncode Inst, Utrecht, Netherlands.
58Peking Univ, Sch Publ Hlth, Dept Occupat & Environm Hlth Sci, Beijing, Peoples R China.
59Univ Med Greifswald, Inst Community Med, Greifswald, Germany.
60Northwestern Univ, Dept Prevent Med, Feinberg Sch Med, Chicago, IL 60611 USA.
61Univ Amsterdam, Amsterdam Univ Med Ctr, Amsterdam Reprod & Dev Res Inst, Dept Clin Genet, Amsterdam, Netherlands.
62Heinrich Heine Univ Dusseldorf, German Diabet Ctr, Leibniz Ctr Diabet Res, Inst Clin Diabetol, Dusseldorf, Germany.
63German Ctr Diabet Res, Munich, Germany.
64Heinrich Heine Univ Dusseldorf, Med Fac, Dept Endocrinol & Diabetol, Dusseldorf, Germany.
65Heinrich Heine Univ Dusseldorf, Univ Hosp Dusseldorf, Dusseldorf, Germany.
66Univ Calif Los Angeles, David Geffen Sch Med, Dept Human Genet, Los Angeles, CA 90095 USA.
67Univ Calif Los Angeles, Fielding Sch Publ Hlth, Biostat, Los Angeles, CA USA.
68Tampere Univ, Fac Med & Hlth Technol, Dept Microbiol & Immunol, Tampere 33014, Finland.
69NHLBI, Div Intramural Res, Populat Sci Branch, NIH, Bethesda, MD USA.
70Imperial Coll London, Sch Publ Hlth, MRC PHE Ctr Environm & Hlth, Dept Epidemiol & Biostat, London, England.
71Univ Oulu, Ctr Life Course Hlth Res, Fac Med, Oulu 90014, Finland.
72Univ Oulu, Bioctr Oulu, Oulu, Finland.
73Oulu Univ Hosp, Unit Primary Care, Oulu, Finland.
74Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48104 USA.
75Univ Tartu, Inst Genom, Estonian Genome Ctr, Tartu, Estonia.
76SYNLAB MVZ Humangenet Mannheim, Mannheim, Germany.
77Tech Univ Munich, Deutsches Herzzentrum Munchen, Munich, Germany.
78DZHK German Ctr Cardiovasc Res, Partner Site Munich Heart Alliance, Munich, Germany.
79Univ Ulm, Inst Epidemiol & Med Biometry, Ulm, Germany.
80Imperial Coll London, Natl Heart & Lung Inst, London, England.
81Loyola Univ Chicago, Dept Publ Hlth Sci, Maywood, IL USA.
82Loyola Univ Chicago, Dept Med, Maywood, IL USA.
83Edward Hines VA Med Ctr, Hines, IL USA.
84Med Univ Innsbruck, Inst Genet Epidemiol, Innsbruck, Austria.
85Tampere Univ, Fac Med & Hlth Technol, Dept Clin Chem, Tampere, Finland.
86Tampere Univ, Fac Med & Hlth Technol, Finnish Cardiovasc Res Ctr, Tampere, Finland.
87Fimlab Labs, Dept Clin Chem, Tampere, Finland.
88Uppsala Univ, Dept Med Sci, Uppsala, Sweden.
89Duke Univ, Sch Med, Dept Med, Div Cardiol,Duke Mol Physiol Inst, Durham, NC 27706 USA.
90Friedrich Schiller Univ Jena, Inst Nutr Sci, Jena, Germany.
91Competence Cluster Nutr & Cardiovasc Hlth nutriCA, Jena, Germany.
92SYNLAB Holding Deutschland GmbH, Synlab Acad, Augsburg, Germany.
93Med Univ Graz, Clin Inst Med & Chem Lab Diagnost, Graz, Austria.
94Univ Med Greifswald, Inst Clin Chem & Lab Med, Greifswald, Germany.
95Ludwig Maximilians Univ Munchen, Munich, Germany.
96Tech Univ Munich, Inst Human Genet, Klinikum Rechts Isar, Munich, Germany.
97Helmholtz Zentrum Munchen, Inst Neurogen, Dept Computat Hlth, Munich, Germany.
98Univ Washington, Dept Hlth Serv, Seattle, WA 98101 USA.
99Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, Turku, Finland.
100Turku Univ Hosp, Dept Clin Physiol & Nucl Med, Turku, Finland.
101Univ Turku, Ctr Populat Hlth Res, Turku, Finland.
102Turku Univ Hosp, Turku, Finland.
103Joslin Diabet Ctr, Boston, MA 02215 USA.
104Harvard Med Sch, Boston, MA 02115 USA.
105Harvard TH Chan Sch Publ Hlth, Dept Environm Hlth, Boston, MA USA.
106Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA.
107Univ Michigan, Inst Social Res, Survey Res Ctr, Ann Arbor, MI USA.
108Univ New South Wales, George Inst Global Hlth, Sydney, NSW, Australia.
109Univ Washington, Inst Publ Hlth Genet, Seattle, WA 98195 USA.
110Univ Groningen, Univ Med Ctr Groningen, Dept Endocrinol, Groningen, Netherlands.
111Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Hanzepl 1, Groningen, Netherlands.
112Helmholtz Zentrum Munchen, Inst Neurogen, Munich, Germany.
113Tech Univ Munich, Chair Neurogenet, Klinikum Rechts Isar, Munich, Germany.
114Munich Cluster Syst Neurol SyNergy, Munich, Germany.
115Med Univ Bialystok, Dept Populat Med & Lifestyle Dis Prevent, Bialystok, Poland.
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 3.8 MB)
Persistent link: http://urn.fi/urn:nbn:fi-fe2022040527177
Language: English
Published: Springer Nature, 2021
Publish Date: 2022-04-05
Description:

Abstract

Chronic kidney disease is a major public health burden. Elevated urinary albumin-to-creatinine ratio is a measure of kidney damage, and used to diagnose and stage chronic kidney disease. To extend the knowledge on regulatory mechanisms related to kidney function and disease, we conducted a blood-based epigenome-wide association study for estimated glomerular filtration rate (n = 33,605) and urinary albumin-to-creatinine ratio (n = 15,068) and detected 69 and seven CpG sites where DNA methylation was associated with the respective trait. The majority of these findings showed directionally consistent associations with the respective clinical outcomes chronic kidney disease and moderately increased albuminuria. Associations of DNA methylation with kidney function, such as CpGs at JAZF1, PELI1 and CHD2 were validated in kidney tissue. Methylation at PHRF1, LDB2, CSRNP1 and IRF5 indicated causal effects on kidney function. Enrichment analyses revealed pathways related to hemostasis and blood cell migration for estimated glomerular filtration rate, and immune cell activation and response for urinary albumin-to-creatinineratio-associated CpGs.

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Series: Nature communications
ISSN: 2041-1723
ISSN-E: 2041-1723
ISSN-L: 2041-1723
Volume: 12
Issue: 1
Article number: 7174
DOI: 10.1038/s41467-021-27234-3
OADOI: https://oadoi.org/10.1038/s41467-021-27234-3
Type of Publication: A1 Journal article – refereed
Field of Science: 3111 Biomedicine
Subjects:
Funding: Acknowledgements and funding sources are listed in the Supplementary Text. Open Access funding enabled and organized by Projekt DEAL.
Copyright information: © The Author(s) 2021. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
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